Summary of Work: Systemic lupus erythematosus (SLE) is an autoimmune disease that can severely damage the kidneys, joints, and other tissues. The role of genetic susceptibility in SLE has been extensively examined, but relatively little is known about the contribution of specific hormonal and environmental influences involved in the etiology of SLE. Our study focuses on measures of endogenous hormone exposure (menstrual and reproductive history), exogenous sources of estrogen (including estrogen replacement therapy and fertility drugs), and occupational exposures that have been linked to the development of SLE or other autoimmune diseases (e.g., silica dust). A population-based case-control study of recently diagnosed patients living in eastern North Carolina and South Carolina is underway: currently 150 cases and 140 controls frequency matched by age, gender, and state are enrolled. Cases are identified through private-practice rheumatologists, 4 university-based rheumatology practices, public health clinics, and patient support groups. Population-based controls are identified through driver's license records. Data collection will continue through June 1998, for a total sample size of 600 (200 cases, 400 controls). A standardized interview includes assessment of previous medical history, family medical history, work and other activities with the potential of exposure to specific materials, and for women, reproductive and menstrual history. Serum is collected to measure specific autoantibodies. White blood cells will be stored for additional studies of gene-environment interactions relating to metabolism, immune function, and hormones.